The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling

Zyulina, Victoria; Ju, Bensheng; Schwarzenberger, Elke; Passegger, Christina; Tam‐Amersdorfer, Carmen; Pan, Qingfei; Sconocchia, Tommaso; Pollack, Christian; Shaner, Bridget; Zebisch, Armin; Easton, John; Yu, Jiyang; Silva, José M.; Strobl, Herbert

doi:10.1016/j.celrep.2021.109049

Cited by 6 publications

(2 citation statements)

References 65 publications

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“…While qRT-PCR results have not shown this in our experiments, an informatics-based sequencing analyses of the control and engineered EV miRNA composition may be required to completely characterize the effect of this type of manipulation. In loss of function experiments, miRNA-424 is reported to be involved in dendritic cell differentiation and pro versus anti-inflammatory switch ( Zyulina et al, 2021 ). However, loss of function studies in relation to bone formation and osteogenesis have not been performed to identify the significance of miRNA-424 to these processes.…”

Section: Discussionmentioning

confidence: 99%

Micro RNA based MSC EV engineering: Targeting the BMP2 cascade for bone repair

Huang

Kang²,

Leung³

et al. 2023

Front. Cell Dev. Biol.

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Mesenchymal stem cell derived extracellular vesicles (MSC EVs) possess excellent immunomodulatory and therapeutic properties. While beneficial, from a translational perspective, extracellular vesicles with consistent functionality and target specificity are required to achieve the goals of precision medicine and tissue engineering. Prior research has identified that the miRNA composition of mesenchymal stem cell derived extracellular vesicles contributes significantly towards extracellular vesicles functionality. In this study, we hypothesized that mesenchymal stem cell derived extracellular vesicle functionality can be rendered pathway-specific using a miRNA-based extracellular vesicles engineering approach. To test this hypothesis, we utilized bone repair as a model system and the BMP2 signaling cascade as the targeted pathway. We engineered mesenchymal stem cell extracellular vesicles to possess increased levels of miR-424, a potentiator of the BMP2 signaling cascade. We evaluated the physical and functional characteristics of these extracellular vesicles and their enhanced ability to trigger the osteogenic differentiation of naïve mesenchymal stem cell in vitro and facilitate bone repair in vivo. Results indicated that the engineered extracellular vesicles retained their extracellular vesicles characteristics and endocytic functionality and demonstrated enhanced osteoinductive function by activating SMAD1/5/8 phosphorylation and mesenchymal stem cell differentiation in vitro and enhanced bone repair in vivo. Furthermore, the inherent immunomodulatory properties of the mesenchymal stem cell derived extracellular vesicles remained unaltered. These results serve as a proof-of-concept for miRNA-based extracellular vesicles engineering approaches for regenerative medicine applications.

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Section: Discussionmentioning

confidence: 99%

Micro RNA based MSC EV engineering: Targeting the BMP2 cascade for bone repair

Huang

Kang²,

Leung³

et al. 2023

Front. Cell Dev. Biol.

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“…Since miRNAs were first discovered in Caenorhabditis elegans in the 1990s, 32 thousands have been identified to date. Many studies have uncovered the important role of miRNAs in regulating skin inflammation and maintaining cutaneous homeostasis, and their dysregulation can lead to pathogenic conditions 17,21,33 . Therefore, a balanced control of miRNAs is key for the normal function of skin tissue.…”

Section: Biogenesis and Function Of Micrornamentioning

confidence: 99%

The role of microRNA in psoriasis: A review

Jiang

Shi

et al. 2023

Experimental Dermatology

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Psoriasis is a chronic immune‐mediated inflammatory skin disease that involves a complex interplay between infiltrated immune cells and keratinocytes. Great progress has been made in the research on the molecular mechanism of coding and non‐coding genes, which has helped in clinical treatment. However, our understanding of this complex disease is far from clear. MicroRNAs (miRNAs) are small non‐coding RNA molecules that are involved in post‐transcriptional regulation, characterised by their role in mediating gene silencing. Recent studies on miRNAs have revealed their important role in the pathogenesis of psoriasis. We reviewed the current advances in the study of miRNAs in psoriasis; the existing research has found that dysregulated miRNAs in psoriasis notably affect keratinocyte proliferation and/or differentiation processes, as well as inflammation progress. In addition, miRNAs also influence the function of immune cells in psoriasis, including CD4+ T cells, dendritic cells, Langerhans cells and so on. In addition, we discuss possible miRNA‐based therapy for psoriasis, such as the topical delivery of exogenous miRNAs, miRNA antagonists and miRNA mimics. Our review highlights the potential role of miRNAs in the pathogenesis of psoriasis, and we expect more research progress with miRNAs in the future, which will help us understand this complex skin disease more accurately.

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